a study of selinexor monotherapy in subjects with jak inhibitor-naïve myelofibrosis and moderate thrombocytopenia

Conditions: Myelofibrosis; Moderate Thrombocytopenia

Summary: the main purpose of this study with corresponding optional expansion is to evaluate the efficacy of selinexor in jaki-naïve participants with myelofibrosis (mf) and moderate thrombocytopenia based on spleen volume reduction (svr). additional efficacy and safety parameters will also be assessed during the study.


Eligibility criteria:
key inclusion criteria: * a diagnosis of mf or post-et or post-pv mf according to the 2016 world health organization (who) classification of mpn, confirmed by the most recent local pathology report. * measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (\>=) 450 cubic square centimeter (cm\^3) by mri or ct scan (results from mri or ct imaging performed within 28 days prior to screening are acceptable). * participants with dipss risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk. * ecog performance status less than or equal to (\<=) 2. * platelet count of 50 to less than (\<) 100 x 10\^9/l without platelet transfusion within 7 days prior to the first dose of selinexor. * absolute neutrophil count (anc) \>=1.0 × 10\^9/l without need for growth factors within 7 days prior to the first dose of selinexor. * adequate liver function as defined by the following: aspartate transaminase (ast) and alanine aminotransferase (alt) \<= 2.5 × upper limit normal (uln) and serum total bilirubin \<= 3×uln. * calculated creatinine clearance (crcl) greater than (\>) 15 milliliter per minute (ml/min) based on the cockcroft and gault formula. * active symptoms of mf as determined by presence of at least 2 symptoms with a score \>= 3 or total score of \>= 10 at screening using the mfsaf v4.0. * participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to c1d1 are permitted) at screening and during the study. * participants currently not a candidate for stem cell transplantation. * participants must be willing to complete the mfsaf v4.0 daily during the study for evaluating the symptom response (i.e., tss50). key exclusion criteria: * more than 10% blasts in peripheral blood or bone marrow (accelerated or blast phase). * previous treatment with jak inhibitors for mf. * previous treatment with selinexor or other xpo1 inhibitors. * female participants who are pregnant or lactating. * prior splenectomy, or splenic radiation within 6 months prior to c1d1. * history of myocardial infarction, unstable angina, percutaneous transluminal coronary angioplasty (ptca) or coronary artery bypass graft (cabg), cerebrovascular accident (stroke or transient ischemic attack \[tia\]), ventricular arrhythmias, congestive heart failure new york heart association (nyha) class \> 2 within 6 months of c1d1. * participants unable to tolerate two forms of antiemetics prior to each dose for the first two cycles.

Keywords: myelofibrosis selinexor total symptom score myelofibrosis symptom assessment form spleen volume reduction tss50 svr35 jak2 kpt-330 pacritinib ruxolitinib momelotinib thrombocytopenia